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ABSTRACT The fundamental objective of military field training exercises (FTX) is to prepare military personnel for real-life operations through simulated scenarios. These training sessions often require extreme physical efforts with prolonged, high-intensity exercises that can be combined with food restrictions and partial, or total, sleep deprivation. Such conditions can compromise an individual’s physical performance and cause tissue damage, thus affecting their health. This study aimed to perform a systematic review of the literature to identify studies that measured the changes in hormone levels and biomarkers of cellular injury and oxidative stress resulting from FTX with high levels of energy expenditure combined with food and sleep restrictions. PubMed and the Scopus database were searched for articles that combined physical effort/food restriction/sleep deprivation with military training. The initial database search identified 158 articles that were reduced to 18 after confirmation. Significant reductions were reported in thyroid hormones, T3, T4, and anabolic hormones such as testosterone, insulin and androstenedione. An exception for GH was found, which increased throughout FTX. Less distinct responses to FTX were observed with cortisol, TSH and LH. The presence of biomarkers for cellular damage (myoglobin, TNF, and CRP) and increased immune response activities were also described. The scarcity of information on oxidative stress, analyses of cellular injury and biomarkers of inflammatory responses warrants the future study of these topics, which could be helpful in facilitating the safe and effective physical preparations of the members of the armed forces.

Abstract Background Unnecessary referrals in Danish hospitals may be contributing to inefficient use of health services already stretched and under pressure and may lead to delayed treatment for patients. Despite a growing awareness in the literature and in practice of issues related to referrals, there has been relatively little research on referrals between specialists in hospital outpatient clinics and how it can be improved. This study aimed to describe the referral patterns to and within the Medical Department at the University Hospital of Southern Denmark. The Medical Department consists of the following medical specialist outpatient clinics; nephrology, pulmonology, endocrinology, cardiovascular, wound outpatient clinic, and a day hospital. Methods Two specialist physicians assessed all referrals to the medical specialist outpatient clinics over one month (from 01 September 2019 to 30 September 2019) using data drawn from the Danish electronic patient record system (Cosmic). Data on referral pattern, and patient age and sex, were statistically analysed to identify and characterise patterns of referral. Results Four hundred seventy-one (100%) referrals were included in the study. 49.5% (233) of the referrals were from the hospital and 50.5% (238) from general practitioners (GPs). Of the 233 referrals from the hospitals, 31% (72) were from the Medical Department. Conclusion The high rate of referrals (31%) from own Medical Department or outpatient clinics may reflect an inefficient internal referral process within the department. Improved collaboration between specialists could have the potential to improve health outcomes, timely access to care and more appropriate healthcare resource utilisation.

Simple Summary: True personalization of internal/general medicine depends on the assessment and acknowledgment of sarcopenia and frailty characteristics of patients. The co-existence of sarcopenia, frailty, and hypothyroidism must be acknowledged by physicians, since these are common comorbidities bearing negative long-term clinical outcomes. Low ALT values could serve as a useful biomarker for screening of patients already diagnosed with hypothyroidism. Background: Hypothyroidism is very common worldwide. It is known to be associated with frailty which, in turn, is associated with increased morbidity and mortality in the elderly. Low ALT blood activity is an established marker for sarcopenia and frailty. The incidence and outcomes of the association between low ALT values and hypothyroidism, as manifested in elevated blood TSH levels, is unknown. The objective of this study was to assess if low ALT values could improve the prediction of clinical outcome in hypothyroid patients. Methods: This was a retrospective analysis of hospitalized patients in a large, tertiary hospital. Results: Over a period of 21 years, an overall population of 16,827 patients were identified as eligible to participate in this study. Within the study population, 726 (4.3%) were classified as suffering from hypothyroidism (TSH values > 6 MIU/L) and 2184 (13%) were classified as patients with sarcopenia (ALT < 12 IU/L). Within our patient population, hypothyroidism was associated with sarcopenia in a statistically significant manner (p = 0.011). Patients classified as suffering from both hypothyroidism and sarcopenia had significantly shorter survival: A multivariate analysis showed that the frail and hypothyroid group of patients had a statistically significant risk of mortality in the next 5 years (HR = 3.6; CI 2.75–4.71; p < 0.001). Conclusions: Sarcopenia and frailty are common comorbidities, bearing negative long-term clinical outcomes. Low ALT values could serve as a useful biomarker for screening of patients already diagnosed with hypothyroidism. [ABSTRACT FROM AUTHOR]

While existing literature on the intersection of trauma and autism is limited, emerging evidence suggests heightened vulnerability of autistic children to the psychological consequences of traumatic events, including an elevated risk of developing posttraumatic stress disorder (PTSD). Additionally, parents of autistic children often experience elevated levels of negative emotional states, compared to parents of typically developing children. This study investigates the impact of terrorism and war on autistic and non‐autistic children and their parents, presenting preliminary results from the initial data collection phase of a year‐long longitudinal investigation of the experience of autistic children and their parents following Hamas' 7 October 2023 attack on Israel. Data gathered within 30 days of the initial attack reveal that both autistic and non‐autistic children exhibited clinically significant post‐traumatic stress symptoms, with autistic children demonstrating a more pronounced manifestation. Moreover, parents of autistic children reported significantly higher levels of depression, anxiety, and stress in the aftermath of the events, compared to an independent cohort of parents of autistic children assessed prior to the crisis. These results underscore the heightened susceptibility of autistic children to post‐traumatic stress and the unique challenges confronted by their parents during times of conflict. The study highlights the imperative for tailored support services for autistic children and their families amidst traumatic incidents and stresses the need for further research in comparable contexts globally. [ABSTRACT FROM AUTHOR]

Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) maintenance. Knockout of Lpl or its obligatory cofactor Apoc2 results in significantly reduced HSPC expansion during definitive hematopoiesis in zebrafish. A human APOC2 mimetic peptide or the human very low-density lipoprotein, which carries APOC2, rescues the phenotype in apoc2 but not in lpl mutant zebrafish. Creating parabiotic apoc2 and lpl mutant zebrafish rescues the hematopoietic defect in both. Docosahexaenoic acid (DHA) is identified as an important factor in HSPC expansion. FFA-DHA, but not TG-DHA, rescues the HSPC defects in apoc2 and lpl mutant zebrafish. Reduced blood cell counts are also observed in Apoc2 mutant mice at the time of weaning. These results indicate that LPL-mediated release of the essential fatty acid DHA regulates HSPC expansion and definitive hematopoiesis.

Resumen: La historia de los inicios en Chile de la implementación nacional de las unidades de cuidados intensivos neonatales, y por ende de los inicios de la neonatología moderna en Chile, es de visionarios motivados exclusivamente por el profundo deseo de mejorar la sobrevida y calidad de vida de pequeños que nacían, muy a su pesar, antes de tiempo. Es una historia que, como muchas otras del desarrollo de la medicina, vale la pena relatar no solo por los logros que alcanzó, sino que también por el proceso de gestación y desarrollo en sí. Recordaremos para ello primero la historia de los orígenes y desarrollo del cuidado de los recién nacidos en el mundo, su avance gradual en el siglo XIX y principios del siglo XX, su consolidación a partir de la década de los 60, y finalmente su impulso en Chile con especial mención de la gestación del programa nacional de cuidados intensivos de prematuros en la década de los 80. Summary: The story of the onset of nationwide implementation of neonatal intensive care units in Chile, and therefore the beginnings of modern neonatology in Chile, is a story of visionaries motivated exclusively by a deep desire to improve the survival rate and quality of life of the little ones who were born, much to their regret, before their time. It is a story that, like many others of advances in medicine, is worth telling not only for the achievements acomplished but also for the gestation and development process itself. We’ll begin this story by recalling the history of the origins and development of newborn care in the world, its gradual growth in the 19th and early 20th centuries, its consolidation from the 1960s onward and finally its development in Chile, with special focus on the gestation of the national program of intensive care for premature infants in the 1980s.

ABSTRACT Objective: To evaluate the impact of pregnancy on differentiated thyroid carcinomas (DTC) behavior Subjects and methods: Retrospective study of patients diagnosed with DTC before or during pregnancy and treated with standard therapy. In women diagnosed with DTC before pregnancy, we evaluated the occurrence of progression according to categories of response to therapy based on imaging and non-stimulated thyroglobulin (TG) levels. Results: Of 96 analyzed patients, 76 became pregnant after DTC treatment and 20 were diagnosed with DTC during pregnancy. Among women who became pregnant after a DTC diagnosis, no difference was observed regarding response to therapy before and after pregnancy. Disease progression after pregnancy was documented in six of these patients, while seven of them presented progression before pregnancy but were only treated after delivery. Patients with DTC diagnosed during pregnancy had a higher rate of distant metastases at diagnosis (30%) compared with the patients who became pregnant after DTC diagnosis (9.2%, p = 0.01). Conclusion: Pregnancy had no impact on the natural course of DTC. Disease progression after pregnancy was limited and probably related to more aggressive disease and higher risk stratification at diagnosis. Still, mild disease progression may have occurred asymptomatically in some patients.

Neutrophils are central players in the innate immune system. To protect against invading pathogens, neutrophils can externalize chromatin to create neutrophil extracellular traps (NETs). While NETs are critical to host defense, they also have deleterious effects, and dysregulation of NETs formation has been implicated in autoimmune diseases, atherosclerosis and thrombotic conditions, cancer progression and dissemination, and acute respiratory distress syndrome. Here, we report that selinexor, a first-in-class selective inhibitor of nuclear export approved for the treatment of multiple myeloma and diffuse large B-cell lymphoma, markedly suppressed the release of NETs in vitro. Furthermore, we demonstrate a significant inhibitory effect of selinexor on NETs formation, but not on oxidative burst or enzymatic activities central to NETs release such as neutrophil elastase, myeloperoxidase or peptidyl arginine deiminase type IV. The inhibitory effect of selinexor was demonstrated in neutrophils activated by a variety of NETs-inducers, including PMA, TGF-β, TNF-α and IL-8. Maximal inhibition of NETs formation was observed using TGF-β, for which selinexor inhibited NETs release by 61.6%. These findings pave the way to the potential use of selinexor in an effort to reduce disease burden by inhibition of NETs.

BackgroundAge is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions.MethodsA total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model.ResultsUsing age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92.ConclusionsA change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.

Macadamia integrifolia is the most economically important Proteaceae crop known for its edible nuts. The present study was conducted to examine the effect of continuous cultivation (for 1, 5, and 20 years) of M. integrifolia on soil quality, bacterial diversity, and metabolites. Soil rhizospheres from three different Macadamia rhizosphere orchards, 1-year monoculture orchard (CK), 5-year monoculture orchard (Y5), and 20-year monoculture orchard (Y20), were analyzed through metagenomic and metabolomic profiling. The soil physicochemical properties, including organic matter, and available nutrients (P, N, and K) were first increased significantly (p < 0.05) from the CK to the Y5 group and then decreased (p < 0.05) from the Y5 to the Y20 group. The soil pH continuously decreased (p < 0.05) over time from CK to Y20. Metagenomic profiling revealed that Actinobacteria, Acidobacteria, and Proteobacteria were the top three abundant phyla with their inconsistent relative abundance patterns from CK to Y20 (CK: 23.76%, Y5: 34. 06%, and Y20: 31.55%), (CK: 13.59%, Y5: 18.59%, and Y20: 21.35%), and (CK: 27.59%, Y5: 15.98%, and Y20: 17.08%), respectively. Furthermore, the Y5 rhizospheres had a higher number of beneficial bacterial genera belonging to Proteobacteria and Actinobacteria than the Y20 rhizospheres. The KEGG annotation analysis revealed that cellular processes, organism systems, metabolism, and genetic information were the most enriched functional categories. CAZy database screening indicated the highest enrichment of glycoside hydrolases following the glycoside transferases and carbohydrate-binding modules. Differential metabolite analysis revealed the highest number of metabolites (11) in the Y5 group than in the Y20 group (6). It is concluded that continuous monoculture of M. integrifolia improves the soil physicochemical properties, bacterial diversity, and metabolite contents in short-term planted orchards which, however, are deteriorated in long-term planted orchards.

ABSTRACT Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. Subjects and methods: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.